Daratumumab

Bristol Myers Squibb said a regimen that includes its experimental drug iberdomide led to no detectable cancer cells in a greater proportion of multiple myeloma patients than those who received standard treatments in a pivotal trial. The New Jersey pharma company appears poised to test the waters of a potential accelerated approval based on the outcome, though it shied away from explicitly saying so in Tuesday’s press release . The pivotal portion of the Phase 3 EXCALIBER-RRMM trial had 664 patients with multiple myeloma that returned or stopped responding to treatment. The participants were given the experimental regimen, which consisted of iberdomide, Johnson & Johnson’s Darzalex and dexamethasone, or the standard regimen of bortezomib alongside the latter two drugs. Bristol Myers said the iberdomide arm had a statistically significant improvement in minimal residual disease (MRD) negativity rates in a planned interim analysis compared to the control group. MRD negativity means there are no detectable cancer cells, though it does not necessarily convey that all cancer cells are gone. An FDA advisory committee last year backed the use of ​​minimal residual disease as an endpoint in accelerated approvals for multiple myeloma drugs. Bristol Myers then changed the design of its study in January to make MRD negativity a dual primary endpoint, according to clinicaltrials.gov . In other words, the study only needs to hit that endpoint or its other primary endpoint of progression-free survival to succeed (as opposed to hitting both endpoints). Other large drugmakers like Gilead have likewise added MRD negativity as a primary endpoint for their multiple myeloma trials in the hopes of hustling their experimental drugs to approval. The FDA has not yet approved any multiple myeloma drugs using MRD negativity as a primary endpoint. Bristol Myers could be the first to ask the FDA to do so. “The company plans to discuss these results with health authorities,” Bristol Myers said. It also noted in the release that “MRD is increasingly being used in clinical trials as a surrogate endpoint for progression-free survival (PFS) and is gaining recognition from regulatory authorities for its role in accelerating therapeutic development.” The company did not immediately respond to a request for comment about its regulatory plans. Iberdomide is a next-generation targeted protein degrader, akin to Bristol Myers’ blockbuster multiple myeloma drug Revlimid. The way Revlimid works — by binding to a part of the body’s natural protein recycling system — was discovered after its approval, and drug developers have since set out to purposefully make new drugs that leverage that system. In multiple myeloma, tagging certain proteins for recycling leads to the death of the cancer cells. Bristol Myers is also developing another protein degrader for multiple myeloma called mezigdomide. The drugmaker said it’s continuing the Phase 3 trial of iberdomide for the other dual primary endpoint of progression-free survival as well as the key secondary endpoint of overall survival. Editor’s note: This story was corrected to note the FDA has not approved any multiple myeloma drugs using MRD as a primary endpoint.

Bristol Myers Squibb scored a much-needed clinical win this year, reporting that its experimental drug iberdomide significantly improved minimal residual disease (MRD) negativity rates compared to controls in a Phase III interim analysis for relapsed or refractory multiple myeloma.The result offers a bright spot for BMS after a string of pivotal study disappointments so far in 2025 that have heightened investor anxiety about the company's pipeline (see – Spotlight On: BMS battles a losing clinical record).Anne Kerber, BMS's head of haematology development, said Tuesday's EXCALIBER-RRMM readout "builds on our significant experience in both targeted protein degradation and developing new treatment options for patients living with multiple myeloma."Iberdomide is the first of a novel class of medicines known as cereblon E3 ligase modulators (CELMoDs) that are designed to harness targeted protein degradation to destroy disease-driving proteins.EXCALIBER-RRMM is comparing iberdomide plus Johnson & Johnson's CD38-directed antibody Darzalex (daratumumab) and dexamethasone against a regimen of Darzalex, bortezomib and dexamethasone in an estimated 864 patients. The interim finding of a statistically significant improvement in MRD negativity — a measure of how thoroughly cancer cells are eradicated — comes as the FDA is weighing whether MRD can support accelerated approvals. An FDA advisory panel last year unanimously backed MRD as a feasible surrogate, and a subsequent FirstWord survey found nearly 90% of US oncologists consider it a reliable predictor of long-term outcomes.At the Morgan Stanley healthcare conference earlier this month, CEO Christopher Boerner struck a cautious note on the FDA's stance toward MRD as a basis for faster approvals. He said the EXCALIBER-RRMM study "is one that we had reviewed with the FDA," but also acknowledged "some new players at FDA now." Boerner said the company is "looking forward to seeing this data and being able to engage with those conversations as the data reads out the way we think it will."The study's other dual-primary endpoint of progression-free survival remains under evaluation, with results expected in 2026.